The initial phase of this project was concerned with describing the CO2 permeability of the proximal tubule. The results showed that: 1) the CO2 permeability approached that of an equivalent thickness of water at rapid luminal perfusion rates, 2) the luminal pH was relatively constant throughout a wide range of perfusion rates when tubules were perfused with isotonic saline, 3) bicarbonate appeared in the luminal perfusate at a rate greater than could be explained by simple diffusion, 4) increasing luminal buffer strength enhanced bicarbonate generation but, 5) bicarbonate was also generated when the luminal buffer was low so that cellular mechanisms for buffering protons had to be invoked to explain the generation of bicarbonate from dissolved CO2. Ion exchanges of Na ion for H ion and Cl minus or OH minus across the luminal membrane could explain the buffering of luminal protons. The effect on luminal total CO2 content was determined when either of these mechanisms was inhibited. In addition, we realized that a parallel array of Na ion/H ion and Cl minus/OH minus exchangers could accomplish neutral NaCl transport across the luminal membrane. Hence, during the second phase of the project, we began to explore the relationships between luminal acidification mechanisms, neutral NaCl transport, and other modes of transcellular sodium reabsorption. These studies will be extended with the isolated, perfused tubule preparation, brush-border vesicle preparation, and the isolated, intact tubule.